Haemolytic Uraemic Syndrome
David V Milford
Paediatric Nephrology for the General Paediatrician 2012
Manchester
Overview
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•
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Presentation
Diagnosis
Management
Prognosis and follow-up
Atypical HUS
Haemolytic uraemic syndromes in childhood
Syndrome comprising
acute renal failure of varying severity
microangiopathic anaemia
thrombocytopenia of varying severity
Multiple aetiologies
BPSU National HUS study 1985-1988
D+
282 (94.6%)
165 (59%)
D16 (5.4%)
9 (56%)
followed for > 4
months
259
15
lone hypertension
CRF
ESRF
died
3
17
0 13.6%
15
2
2
5
3
reported
dialysed
Arch. Dis. Child 1990; 65:716-721
78%
Arch. Dis. Child 1990; 65:716-721
Evolution of lab results
in HUS – outbreak in an
institution
Diagnosis
• Diarrhoea (often bloody)
• Haematological – microangiopathic haemolytic
anaemia
- thrombocytopenia
Fragmented red cells
Absence of platelets
Acute Kidney Injury
Shiga toxin producing E.coli (STEC) isolates
BAPN/CDC study 1985-88
isolates
VTEC
O157
HUS
185
60
39
Bloody diarrhoea
48
4
3
Diarrhoea
54
3
1
Controls
46
2
0
Arch. Dis. Child. 1990; 65:722-727
D+ HUS and EHEC
• EHEC colonise cattle
• Transmission – contaminated meat, milk,
water, fruit, vegetables
• Exposure to EHEC → diarrhoea in ≈ 10%
children
• HUS develops in ≈ 15% of children with EHEC
diarrhoea
• O157:H7 predominant serotype in the UK
– O26:H11, O103:H2, O111:NM, O121:H19, O145:NM
Annual STEC cases in the UK
Emerging Infectious Diseases 2005; 11: 590-6
Non-renal complications
• Seizures
– hyponatraemia
– neurotoxicity (STx receptors – neurones,
endothelium)
• Hypertension
• Gut
– rectal prolapse
– toxic megacolon, perforation, intussception
• Cardiomyopathy
• Diabetes mellitus
Acute CNS changes
6 months
Even in patients with severe CNS involvement on
acute imaging studies, prognosis can be favourable for
clinical outcome and resolution of pathological imaging
findings
Pediatr Radiol (2004) 34: 805–810
Clin J Am Soc Nephrol 2010; 5:1218–1228,
Rectal prolapse
Air in bowel
Late change - stricture
Emerging Infectious Diseases 2005; 11: 590-6
Infections in HUS 1997-2001
395 D+ HUS
1 O26
65
18 D- HUS
329 (83%) O157 +ve
culture/serology
No infection identified 59
S pneumonae 7
Campylobacter 2
Shigella Sonnei 1
S pneumonae 1
Staph aureus 1
Emerging Infectious Diseases 2005; 11: 590-6
CKD 1
Died 2
(out of 8 cases)
Northern German outbreak May-July 2011
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•
•
•
Source: bean sprout farm in Lower Saxony
Sprouted from batch of seeds from Egypt
3793 cases of diarrhoea – O104:H4
Delay in symptoms, ingestion → diarrhoea 8
days
• 827 (22%) developed HUS, 88% in adults
• 53 deaths
• 2010 European data
– 4000 STEC cases reported, 5.5% developed HUS
– O157 (41%), 026 (7%), O103 (2.5%)
Management
• Conservative
– Monitor fluid balance, sodium, potassium, H+,BP
– Furosemide may be useful early
– Sodium, protein restriction; high calorie intake
– Transfuse with caution
– Avoid antibiotics/anti-motility agents/NSAID
• Transfer to regional centre
– Oliguria +
• Fluid overload, need for transfusion, high K
– Anuria
– Complications of D+ HUS
Prognosis and follow-up
• BCH (n=250) 56% required acute dialysis
• Prognostic markers
– Neutrophils >20 at presentation
– Dialysis > 2weeks
• Mortality
– 5% (BPSU 1985-88)
– 1.8% (BPSU 1997-2001)
• Long term: HBP, reduced GFR, proteinuria
– Variable in studies, probably 20-30%
– BCH n=201 19% poor outcome at 5,10,0r 15 yrs
Proteinuria at 1 year and outcome
Poor outcome
Good outcome
J Pediatr 1991; 118:191-4
• Follow-up
– Frequently until Hb and creatinine normal
– BP, PCr and EMU protein at 1 year after illness
– BP, EMU protein, formal GFR, renal USS at 5 years
and every 5 years until post pubertal
– BP, EMU protein by GP at intervals once
discharged
• Lifestyle advice
– Avoid overweight, high sodium intake
– Avoid smoking
– Girls need renal function/proteinuria monitoring
during pregnancy
Level 1: aetiology advanced
1.i Infection induced
(a) Shiga and shiga-like toxin-producing bacteria;
enterohaemorrhagic Escherichia coli, Shigella
dysenteriae type 1, Citrobacter freundii
(b) Streptococcus pneumoniae, neuraminidase and
T-antigen exposure
1.ii Disorders of complement regulation
(a) Genetic disorders of complement regulation
(b) Acquired disorders of complement regulation, e.g.
anti-factor H antibody
1.iii von Willebrand proteinase, ADAMTS13,
deficiency
(a) Genetic disorders of ADAMTS13
(b) Acquired ADAMTS13 deficiency; autoimmune,
drug induced
1.iv Defective cobalamin metabolism
1.v Quinine induced
Level 2: aetiology unknown
2.i Human immunodeficiency virus (HIV)
2.ii Malignancy, cancer chemotherapy and ionising
radiation
2.iii Calcineurin inhibitors and transplantation
2.iv Pregnancy, HELLP syndrome and oral
contraceptive pill
2.v Systemic lupus erythematosus and antiphospholipid
antibody syndrome
2 vi Glomerulopathy
2.vii Familial, not included in part 1
2.viii Unclassified
Typical/diarrhoeal/
D+ HUS
Atypical/
non-diarrhoeal/
D- HUS
Alternative complement pathway
Johnson, Eur J Pediatr 2008:167;965–971
Non-diarrhoeal HUS
• Requires urgent referral to a nephrology
centre
• Associated with
– High risk of death, CKD, hypertension, CNS events,
recurrent episodes, familial
• Therapies used
– Plasmapheresis
– Plasma infusion (especially ADAMTS13)
– Eculizumab (binds to C5 and blocks C5 convertase)
– Liver, liver/kidney transplantation
QUESTIONS?
Glomerular size in HUS patients with proteinuria
3.3-7 years after illness
n=7
J Pediatr 1998; 133:220-3